Bafetinib in Treating Patients With Recurrent High-Grade Glioma or Brain Metastases

NCT01234740 | Completed Phase 1 DMC

• 2 other identifiers: 10134NCI-2010-01963
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 2

Brief Summary

RATIONALE: Bafetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. PURPOSE: This clinical trial studies bafetinib in treating patients with recurrent high-grade glioma or brain metastases.

Conditions

Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Recurrent Adult Brain Tumor; Tumors Metastatic to Brain; Adult Anaplastic Oligoastrocytoma

Keywords

Los Angeles

Outcome Measures

Primary Outcomes (4)

• Area-under-the-concentration-time-curve (AUC) of bafetinib in dialysate

  every hour for 24 hours after first dose of bafetinib

• Peak concentration (Cmax) of bafetinib in dialysate

  every hour for 24 hours after first dose of bafetinib

• AUC of bafetinib in plasma

  1, 2, 3, 4, 6, 8, and 12 hours after the first dose of bafetinib and then 1, 2, 3, 4, 6, 8, and 12 hours after the second dose of bafetinib

• Cmax of bafetinib in plasma

  1, 2, 3, 4, 6, 8, and 12 hours after the first dose of bafetinib and then 1, 2, 3, 4, 6, 8, and 12 hours after the second dose of bafetinib

Secondary Outcomes (5)

• Determination of adverse events associated with bafetinib in patient with recurrent malignant brain tumors

  30 days after last dose of bafetinib

• Response rate in patients with malignant brain tumors treated with bafetinib

  30 days after last dose of bafetinib

• Progression-free survival in patients with malignant brain tumors treated with bafetinib

  1 year after last dose of bafetinib

• Overall survival in patients with malignant brain tumors treated with bafetinib

  2 years after last dose of bafetinib

• Assessment for expression of Lyn and Fyn kinases and phosphorylation status in pre-treatment tumor samples.

  Pre-treatment tumor samples

Study Arms (1)

Arm I

EXPERIMENTAL

Patients undergo intracerebral microdialysis during debulking craniotomy or stereotactic biopsy. Beginning 24 hours later, patients receive oral bafetinib twice daily for 1 day. Beginning at least 2 weeks after surgery, patients continue to receive oral bafetinib twice daily in the absence of disease progression or unacceptable toxicity.

Drug: bafetinib; Procedure: microdialysis; Other: pharmacological study; Other: liquid chromatography; Other: mass spectrometry; Other: laboratory biomarker analysis; Genetic: protein expression analysis; Genetic: western blotting; Other: immunohistochemistry staining method; Procedure: therapeutic conventional surgery

Interventions

bafetinib DRUG

Given orally

Also known as: dual Bcr-Abl/Lyn tyrosine kinase inhibitor INNO-406, INNO-406, NS-187

Arm I

microdialysis PROCEDURE

Catheter placed intracerebrally during debulking craniotomy or stereotactic biopsy

Arm I

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Arm I

liquid chromatography OTHER

Correlative studies

Also known as: LC

Arm I

mass spectrometry OTHER

Correlative studies

Arm I

laboratory biomarker analysis OTHER

Correlative studies

Arm I

protein expression analysis GENETIC

Correlative studies

Arm I

western blotting GENETIC

Correlative studies

Also known as: Blotting, Western, Western Blot

Arm I

immunohistochemistry staining method OTHER

Correlative studies

Also known as: immunohistochemistry

Arm I

therapeutic conventional surgery PROCEDURE

debulking craniotomy

Arm I

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have radiographic findings consistent with either:
• Recurrent high-grade glioma, or
• Metastatic disease to the brain that has progressed after treatment with whole brain radiation therapy or stereotactic radiosurgery; patients who have a resectable brain metastasis as the only site of disease (i.e., no evidence of systemic disease), are not eligible to participate
• Patients who are in need of a surgical debulking or a stereotactic biopsy for the purpose of diagnosis or differentiating between tumor progression versus treatment-induced effects following radiation therapy +/- chemotherapy will be eligible to participate in the microdialysis part of the study prior to beginning cycle 1 of bafetinib if the study neurosurgeon thinks there is a likelihood of being able to place the microdialysis catheter into residual tumor (enhancing brain tissue)
• Patients who choose not to participate in the microdialysis part of the study may enroll in the study and start treatment at cycle 1 of bafetinib
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for 3 months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
• Patients must have a Karnofsky Performance Status (KPS) \>= 60%
• If corticosteroids are required for controlling cerebral edema, patients must be on a stable dose for at least 1 week prior to enrollment
• Patients must not be taking any hepatic enzyme-inducing anticonvulsants (phenytoin, carbamazepine, phenobarbital, primidone, oxcarbazepine) for at least 2 weeks prior to enrollment
• Absolute neutrophil count \>= 1500 cells/mm\^3
• Platelet count \>= 100,000 cells/mm\^3
• Total bilirubin =\< 2.0 mg/dl
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) =\< 3 times the institutional upper limit of normal
• Alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase \[SGPT\]) =\< 3 times the institutional upper limit of normal
• Serum creatinine =\< 1.5 x the institutional upper limit of normal

You may not qualify if:

• Patients who are currently receiving chemotherapy or are enrolled in another treatment clinical trial
• Patients with a coagulopathy or bleeding disorder
• Patients on anticoagulant drug therapy or medications that inhibit platelet function, such as ibuprofen or other non-steroidal anti-inflammatory drugs
• Clinically evident congestive heart failure \> class II of the New York Heart Association (NYHA) guidelines
• Clinically significant cardiac arrhythmias
• Patients taking a drug that can prolong the QT interval; if a potential study patient is taking one of the prohibited drugs but s/he can safely stop it, then a washout period of \>= 7 days is required prior to starting bafetinib
• History or signs of active coronary artery disease with or without angina pectoris
• Patients who have a serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol or may not be able to comply with the safety monitoring requirements of the study
• Human immunodeficiency virus (HIV)-positive patients receiving anti-retroviral therapy are excluded from the study due to the possibility of pharmacokinetic (PK) interactions with bafetinib; however, patients will not be routinely screened for HIV
• Female patients who are pregnant or breast-feeding
• Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals or anti-fungals
• Patients who have not recovered from the toxicities of prior chemotherapy or radiotherapy

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

South Pasadena Cancer Center

South Pasadena, California, 91030, United States

Location

Related Publications (1)

• Portnow J, Badie B, Markel S, Liu A, D'Apuzzo M, Frankel P, Jandial R, Synold TW. A neuropharmacokinetic assessment of bafetinib, a second generation dual BCR-Abl/Lyn tyrosine kinase inhibitor, in patients with recurrent high-grade gliomas. Eur J Cancer. 2013 May;49(7):1634-40. doi: 10.1016/j.ejca.2013.01.001. Epub 2013 Feb 4.

  PMID: 23380277 DERIVED

MeSH Terms

Conditions

Astrocytoma; Ependymoma; Oligodendroglioma; Glioblastoma; Gliosarcoma; Glioma; Brain Neoplasms

Interventions

bafetinib; Microdialysis; Chromatography, Liquid; Mass Spectrometry; Blotting, Western; Immunohistochemistry

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Dialysis; Chemistry Techniques, Analytical; Investigative Techniques; Chromatography; Electrophoresis; Electrochemical Techniques; Immunoblotting; Immunoassay; Immunologic Techniques; Molecular Probe Techniques; Histocytochemistry; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques

Study Officials

• Jana Portnow

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2010
• First Posted: November 4, 2010
• Study Start: December 1, 2010
• Primary Completion: March 1, 2013
• Study Completion: March 1, 2013
• Last Updated: April 17, 2018

Record last verified: 2018-04

Locations

US (2)